Cancers of the esophagus (squamous cell carcinoma and adenocarcinoma) and the gastric cardia are known to have a poorer prognosis than most other cancers. Concordant observations from the U.S. and western Europe indicate that adenocarcinoma of the esophagus and gastric cardia show among the most sharply rising incidence rates of all cancers. Therefore, there is an urgent need for analytic epidemiologic studies that may disclose causative factors. Our long-term objective is to increase our understanding of the etiologies of these cancers, and to identify etiologically important risk factors which may be potentially amenable to preventive measures. The specific aims also include an investigation of whether similar or different factors are conducive to the occurrence of the three cancer types (squamous cell carcinoma of the esophagus, adenocarcinoma of the esophagus, and adenocarcinoma of the gastric cardia. Moreover, we intend to analyze by means of high diagnostic standards whether indeed the apparent rise in the incidence of adenocarcinomas of the esophagus may be due merely to a true increase in the occurrence of cardia cancer, some of which are misclassified as having originated in the esophagus. We propose a population-based case- control study over a 4-year period with face-to-face interviews of approximately 300 patients with squamous cell cancer of the esophagus, 120 patients with adenocarcinoma of the esophagus, and 360 patients with cancer of the gastric cardia. Approximately 780 population-based controls will also undergo interview. The source population will comprise entire Sweden. A network of contact persons at all departments involved in the diagnosis or management of the cancers under study will ensure prompt identification of all new cases, and a network of professional interviewers will carry out the interviews without delay, preferably before any surgical intervention takes place. The research hypotheses to be tested relate among other things to dietary exposures to potentially harmful (protein, carbohydrates, cholesterol, salt, N- nitroso compounds, moldy food, hot drinks polycyclic aromatic hydrocarbons) and possibly protective (vegetables, fruits, vitamins A, B2, C and E, nicotinic acid, iron, magnesium, zinc, molybdenum) nutrients, occupational exposures (notably metal dust, rubber vulcanization work and toxic halogenated aromatic compounds), the occurrence of symptoms of gastroesophageal reflux, tobacco smoking, alcohol use, and snuff dipping. Univariate, stratified and multivariate analyses will be carried out using standard epidemiologic methods with the relative risk as the central measure of association.